Description: <b><a href="https://en.wikipedia.org/wiki/Methylglyoxal">Methylglyoxal</b></a> is a reduced derivative of pyruvic acid that is produced by glycolysis and other metabolic pathways. It is involved in the formation of advanced glycation end products, DNA damage, and diabetes complications.<br>
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-Methylglyoxal is specifically inhibits OXPHOS in cancer cells ?<br>
-Methylglyoxal in cancer cells inhibits GAPDH, an essential enzyme acting in the glycolsis pathway. GAPDH inhibition depletes ATP profoundly depriving the cancer cells of energy. <br>
-Activator of GABA A receptor<br>
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<a href="https://www.cancertreatmentsresearch.com/methilglyoxal/" >Some research may indicate it can promote cancer growth.</a><br>
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Dose: (30-40mg/day) 7.5mg/kg 4 times/day (plus 400mg Vit C) + VitB complex twice/day <br>
-Combine with curcumin(8g/d)?<br>
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Combine with:<br>
Chitosan?<br>
Creatine (30-60 mins before)<br>
GLO1 inhibitors (Naringin, Curcumin)<br>
Nrf2 inhibitors: (ex Ascorbic Acid)<br>
GABA supplementation<br>
Metformin?<br>
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Avoid combination with DCA?<br>
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Pathways<br>
1. Glyoxalase System
Glyoxalase I and II: (glyoxalase system) which detoxifies methylglyoxal. In many cancers, the expression of glyoxalase I (and sometimes glyoxalase II) is upregulated. This allows tumor cells to tolerate higher MG levels resulting from their altered metabolism (often enhanced glycolysis), protecting them from dicarbonyl stress while simultaneously supporting their survival and proliferation.<br>
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2. Advanced Glycation End Products (AGEs) and RAGE Pathway<br>
AGE Formation:-Supplemented MG can increase the formation of advanced glycation end products (AGEs)
RAGE Activation:AGEs can lead to the activation of RAGEE, which include the activation of NF-κB and MAPK pathways. <br>
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3. NF-κB Signaling Pathway: The activation of NF-κB by MG-induced AGE-RAGE signaling <br>
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4. MAPK Pathway: can be activated as a result of MG-induced oxidative and dicarbonyl stress<br>.
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5. ROS Generation and Oxidative Stress<br>
Methylglyoxal can raise intracellular ROS levels. (reinforcing the pro-tumorigenic environment.)
-excessive ROS can be deleterious. <br>
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Sources:
<a href="https://www.scbt.com/p/methylglyoxal-solution-78-98-8" >Western or Chinese chemical suppliers under CAS number 78-98-8 </a> <br>